In this project, the PMN function altering and anti-inflammatory characteristics of human colostrum/milk will be examined. The studies proposed will characterize the colostrum/milk components responsible for altering human PMN function and the mechanisms by which these effects occur. In addressing mechanisms, changes in both cellular phenotype and gene expression that result from colostrum exposure will be examined. Studies will also characterize the anti-inflammatory components of human colostrum/milk using a rat model of acute inflammation, and examine the mechanisms by which the anti-inflammatory effects are mediated. These mechanistic studies will focus on (but not be limited to) neutralization of pro-inflammatory cytokine activities. Field studies will be used to prospectively examine the relationship between the content and activity of milk anti-inflammatory components and the occurrence of asymptomatic, mild-symptomatic and inflammatory-symptomatic enteric infections. By completion of these studies, we will concretely associate the PMN function-altering and anti-inflammatory characteristics of human colostrum/milk with protection against inflammatory enteric diseases in breastfed infants.